Abstract

Sleeping sickness is a fatal disease caused by Trypanosoma brucei, a unicellular parasite that lives in the bloodstream and interstitial spaces of peripheral tissues and the brain. Patients have altered sleep/wake cycles, body temperature, and endocrine profiles, but the underlying causes are unknown. Here, we show that the robust circadian rhythms of mice become phase advanced upon infection, with abnormal activity occurring during the rest phase. This advanced phase is caused by shortening of the circadian period both at the behavioral level as well as at the tissue and cell level. Period shortening is T. brucei specific and independent of the host immune response, as co-culturing parasites with explants or fibroblasts also shortens the clock period, whereas malaria infection does not. We propose that T. brucei causes an advanced circadian rhythm disorder, previously associated only with mutations in clock genes, which leads to changes in the timing of sleep.

Details

Title
Sleeping sickness is a circadian disorder
Author
Rijo-Ferreira, Filipa 1   VIAFID ORCID Logo  ; Carvalho, Tânia 2 ; Afonso, Cristina 3 ; Sanches-Vaz, Margarida 2 ; Costa, Rui M 3 ; Figueiredo, Luísa M 2   VIAFID ORCID Logo  ; Takahashi, Joseph S 4   VIAFID ORCID Logo 

 Graduate Program in Areas of Basic and Applied Biology, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA 
 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal 
 Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Lisbon, Portugal 
 Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA 
First page
1
Publication year
2018
Publication date
Jan 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1984759482
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.